Effect of the H2 antagonist cimetidine versus famotidine on serum theophylline level and theophylline induced hypokalemia in rats

ABSTRACT

The effect of the H[2] antagonists on serum theophylline level was determined both directly by measuring serum theophylline concentrations at 0.5 - 1 - 2 - 4 and 6 hours after a single therapeutic dose of the drug [l0mg/kg intraperitoneally [IP]] in control [untreated] rats and in rats pretreated with Cimetidine [100 mg/kg] or famotidine [4 mg/kg] orally for 1 week and indirectly by determining the influence of these H[2] antagonists [in the above doses] on the degree of hypokalemia induced by a single high dose of theophylline [25 mg/kg Ip] [theophylline induced hypokalemia is believed to correlate well with serum theophylline level]. The results showed that Cimetidine consistently induced a statistically significant increase in serum theophylline level starting 1 hour after injection [10.3% [P<0.05] and thereafter [40.6 - 41.6 and 45.2% at 2-4 and 6 hours respectively [P<.0005]]. In contrast famotidine did not induce significant changes in serum theophylline level [P>.05] during the total duration of the experiment. Moreover, high dose theophylline induced a statistically significant reduction [P<.0005] in serum K+ from a control value of 3.9 +/- .06 to 3.5 +/- .047 mEq/L [10.25%]; pretreatment with Cimetidine resulted in a further reduction in serum K+ from 3.5 +/- .047 to 3.2 +/- 0.04 mEq/L [8.5% P<.0005] whereas pretreatment with famotidine resulted in an insignificant change [3.5 +/- .047 versus 3.4 +/- 0.07 mEq/L 2.8%P>.05]. Since H [2] receptor antagonists and theophylline may be given concurrently in more than one clinical setting [prophylactic against development of gastrointestinal symptoms of theophylline, in reflux oesophagitis occurring in as many as 30-60% of asthmatics or in patients with upper gastrointestinal bleeding who are intubated and maximally bronchodilated], clinicians should be alert to the significant interaction. Serum theophylline concentration should be measured periodically, measurement of serum potassium could also assist indirectly in prediction of serum theophylline level. Finally famotidine could be a safer alternative to cimetidine whenever H[2] antagonists are given concurrently with theophylline